TAAR1 Membrane Protein Introduction

Introduction of TAAR1

Trace amine-associated receptor 1 (TAAR1) is a trace amine-associated receptor (TAAR) protein that in humans is encoded by the TAAR1 gene. The human TAAR1 gene is thought to be an intronless gene which was discovered in 2001 by two independent groups of investigators. TAAR1 is an intracellular amine-activated Gs-coupled and Gq-coupled G protein-coupled receptor (GPCR). So, it shares structural similarities with the class A rhodopsin GPCR subfamily. And it has 7 transmembrane domains with short N and C terminal extensions. TAAR1 is 62–96% identical with TAARs2-15, which suggests that the TAAR subfamily has recently evolved. At the same time, the low degree of similarity between TAAR1 orthologues suggests that they are rapidly evolving. TAAR1 shares a predictive peptide motif with all other TAARs.

Function of TAAR1 Membrane Protein

TAAR1 is one of the six functional human trace amine-associated receptors, which are so named for their ability to bind endogenous amines that occur in tissues at trace concentrations. TAAR1 plays a significant role in regulating neurotransmission in dopamine, norepinephrine, and serotonin neurons in the CNS. It also affects the immune system and monoaminergic systems function through different mechanisms. In the immune system, TAAR1 transmits signals through active PKA and PKC phosphorylation cascades. Some study observed that methamphetamine had these effects, suggesting that, in addition to brain monoamine regulation, amphetamine-related compounds may have an effect on the immune system. And a recent paper showed that, along with TAAR1, TAAR2 is required for full activity of trace amines in PMN cells. In monoaminergic systems, one of the downstream effects of active TAAR1 is to increase cAMP in the presynaptic cell via Gαs G-protein activation of adenylyl cyclase. This alone can have a multitude of cellular consequences.

Fig.1 Structure of TAAR1 membrane protein.

Application of TAAR1 Membrane Protein in Literature

1. Shi X., et al. Genetic Polymorphisms Affect Mouse and Human Trace Amine-Associated Receptor 1 Function. PloS one. 2016, 11(3):e0152581. PubMed ID: 27031617.
   
   

   This article demonstrates that SNPs in human TAAR1 alter its function, resulting in expressed, but functional, sub-functional and non-functional receptors. Their findings are important for identifying a predisposition to human diseases, as well as for developing personalized treatment options.

2. Panas M.W., et al. Trace amine associated receptor 1 signaling in activated lymphocytes. Journal of neuroimmune pharmacology. 2012, 7(4):866-76. PubMed ID: 22038157.
   
   

   This article proves that an increase in TAAR1 receptor expression is concomitant with lymphocyte immune activation, suggesting a possible role for TAAR1 in the generation or regulation of an immune response. And TAAR1 is emerging as a potential therapeutic target, with regard to its ability to modulate brain monoamines.

3. Espinoza S., et al. Functional interaction between trace amine-associated receptor 1 and dopamine D2 receptor. Molecular pharmacology. 2011, 80(3):416-25. PubMed ID: 21670104
   
   

   This article suggests that TAAR1 and D2R have functional and physical interactions that could be critical for the modulation of the dopaminergic system by TAAR1 in vivo.

4. Babusyte A., et al. Biogenic amines activate blood leukocytes via trace amine-associated receptors TAAR1 and TAAR2. Journal of leukocyte biology. 2013, 93(3):387-94. PubMed ID: 23315425.
   
   

   This article demonstrates that biogenic amines potently regulate blood cell functions via TAAR1 and TAAR2 and open the perspective of their specific pharmacological modulation.

5. Miller G.M. The emerging role of trace amine-associated receptor 1 in the functional regulation of monoamine transporters and dopaminergic activity. Journal of neurochemistry. 2011, 116(2):164-76. PubMed ID: 21073468.
   
   

   This overview focuses on recent studies which reveal a role for TAAR1 in the functional regulation of monoamine transporters and the neuronal regulatory mechanisms that modulate dopaminergic activity.

TAAR1 Preparation Options

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